Study of Efficacy and Safety of MIJ821 in Addition to Comprehensive Standard of Care on the Rapid Reduction of Symptoms of Major Depressive Disorder in Subjects Who Have Suicidal Ideation With Intent

Phase 2TerminatedNCT04722666

Novartis Pharmaceuticals199 enrolled

Overview

Study of efficacy and safety of MIJ821 in addition to comprehensive standard of care on the rapid reduction of symptoms of Major Depressive Disorder (MDD) in subjects who have suicidal ideation with intent

The main purpose of this study was to support the dose selection for future Phase III clinical trials by evaluating efficacy and safety of four MIJ821 doses (very low, low, high and very high) administered every other week for 6 weeks (3 infusions) by intravenous infusion on top of pharmacological antidepressant treatment, compared with placebo, for the rapid reduction of the symptoms of MDD in participants who have suicidal ideation with intent. In addition, the study explored the effect of single dose administration of very high and high doses to treat MDD in participants who have suicidal ideation with intent. The study consisted of three periods: a Screening Period (up to 48 hrs), a double-blind Core Period (6 weeks) and Extension Period (up to 52 weeks). The Extension Period explored durability of the effect of the study treatment and the effect of MIJ821 on relapse rate, as well as safety of MIJ821 administration. Those patients that responded to treatment at the end of the Core period were followed for up to a 52-week Extension period and were allowed to be retreated due to a relapse once with the same active treatment regimen as in the Core period (participants treated with placebo in the Core period were randomly switched to an MIJ821 regimen).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

199

Conditions

Major Depressive Disorder With Suicidal Ideation With Intent

Interventions

MIJ821 Intravenous InjectionDRUG

MIJ821 supplied in vials to be prepared on a mg/kg basis and to be administered for 40 minutes IV infusion on Day 1, Day 15 and Day 29

Placebo Intravenous InjectionDRUG

40 minutes IV infusion of 0.9% sodium chloride solution on Day1, Day 15 and Day 29

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signed informed consent must be obtained prior to participation in the study 2. Male and female participants, 18 to 65 years of age (inclusive) at screening 3. DSM-5 defined major depressive disorder (MDD) with a current major depressive episode (MDE) without psychotic features at the time of screening based upon clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I.) assessed at Screening 4. Participants must have current suicidal ideation with intent, confirmed by a "Yes" response to Question B3 AND either Question B10 or Question B11 obtained from the M.I.N.I., assessed at Screening 5. Current suicidal ideation with intent, confirmed by "Yes" response to Question 3 AND either Question 9 or Question 10 obtained from the SSTS at Baseline 6. Montgomery-Åsberg Depression Rating Scale (MADRS) score \> 28 at Screening and before randomization on Day 1 7. Participants must agree to receive pharmacological standard of care treatment to treat their MDD (as determined by the treating physician(s) based on clinical judgement and local treatment guidelines) during the trial duration 8. In the physician's opinion, acute psychiatric hospitalization is clinically warranted to treat the patient's condition, and the patient is either already in the hospital or agrees to be hospitalized voluntarily for the required per protocol period Exclusion Criteria: 1. Any prior or current diagnosis of bipolar disorder, MDD with psychotic features, schizophrenia, or schizoaffective disorder as obtained from M.I.N.I. at Screening 2. Patients with acute alcohol or substance use disorder or withdrawal symptoms requiring detoxification, or patients who went through detoxification treatment (inpatient or outpatient) within 1 month before Screening. 3. Participant has a current clinical diagnosis of autism, dementia, or intellectual disability 4. History of seizures. Note: childhood febrile seizures are not exclusionary 5. Participants with current borderline personality disorder as obtained from M.I.N.I. at Screening. 6. Participants with suicidal ideation or behavior caused primarily by another non-MDD condition as obtained from M.I.N.I. at Screening 7. Participants taking medications prohibited by the protocol 8. Intake of the following medications/ psychotherapy: 1. Esketamine or Ketamine 2 months before Screening 2. Current Monoamine oxidase inhibitors (MAOIs) 14 days before Screening 3. known worsening or new appearance of suicidal ideation or behavior during a prior treatment, or within 2 months after last administration 9. Any other condition (e.g. known liver disease/liver dysfunction, active malignancy, etc.) which in the opinion of the investigator would put the safety of the participant at risk, impede compliance or hinder completion of the study.

Locations (39)

Outcomes

Primary Outcomes

Change From Baseline in the Total Score of the Montgomery Åsberg Depression Rating Scale (MADRS)

The Montgomery Åsberg Depression Rating Scale (MADRS, SIGMA version), is a clinician rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 0 - 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts and suicidal thoughts. The MADRS was collected electronically by qualified personnel. Since the MADRS total score at 24 hours was evaluated post the single first infusion (prior to the second infusion), the bi-weekly and single dosing regimens of the same dose level are pooled as one arm for 0.048 mg/kg and 0.16 mg/kg.

Time frame: Baseline, 24 hours

Secondary Outcomes

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESI) During the Core Period

Treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESIs) in Core period

Time frame: 6 weeks

AUClast - Pharmacokinetics (PK) of MIJ821 in Plasma

AUClast of MIJ821 in plasma after 1st infusion. AUClast is the Area Under the Curve (AUC) from time zero to the last measurable concentration sampling time (tlast). Since PK was evaluated post the single first infusion, the bi-weekly and single dosing regimens of the same dose level are pooled as one arm for 0.048 mg/kg and 0.16 mg/kg.

Time frame: Pre-dose, 20min, 40min, 4hours and 24hours post 1st infusion

Cmax - Pharmacokinetics (PK) of MIJ821 in Plasma

Cmax of MIJ821 in plasma after 1st infusion. AUClast is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration. Since PK was evaluated post the single first infusion, the bi-weekly and single dosing regimens of the same dose level are pooled as one arm for 0.048 mg/kg and 0.16 mg/kg.

Data from ClinicalTrials.gov

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